Bluebird's Gene Therapy Cures Blood Disorder In Phase 1/2 Trial

Gene therapy company, Bluebird Bio, has announced exciting results of its LentiGlobin BB305 drug product in a Phase 1/2 study in patients with beta-thalassemia major, a deadly genetic blood disorder. Of the four trial subjects treated with LentiGlobin BB305 and followed for at least three months, all four were found to be producing sufficient hemoglobin on their own to eliminate the need for blood transfusions — the standard treatment for these patients.

The results were presented at the American Society of Hematology’s (ASH) 56th Annual Meeting in San Francisco this week.

Bluebird Bio’s ongoing, open-label Phase 1/2 study with LentiGlobin has enrolled a total of eight patients so far: five in the U.S. trial arm (Northstar), and three in Europe (HGB-205). The results presented by Bluebird are from two patients in each of those studies, who have had at least three months of follow-up since being treated with LentiGlobin.

The 2 patients in the U.S. trial have been transfusion-free for three and five months, while the 2 patients in the Europe trial arm have gone for nine and 12 months without transfusions. The remaining patients in the study are still at an early stage and will be assessed in coming months, says Bluebird.

Alexis A. Thompson, M.D., M.P.H., professor of pediatrics at Northwestern University and lead investigator of the Northstar Study, said, “Data from the Northstar Study presented today further demonstrate the potential for a one-time gene therapy treatment to transform the lives of patients with beta-thalassemia major, including those with the most severe genotype of beta-thalassemia major, beta-0/beta-0, also known as Cooley’s Anemia.”

Patients with beta-thalassemia are unable to produce enough of the oxygen carrier, hemoglobin, thus resulting in severe anemia. Nearly 40,000 children worldwide are born with a serious form of the disease every year, and most do not live past age forty without aggressive treatment. The standard treatment for this condition is regular blood transfusions for their entire lives, which unfortunately leads to several other complications such as fatigue, joint pain, liver cirrhosis, and heart failure.

The LentiGlobin BB305 gene therapy product treats beta-thalassemia major through autologous stem cell transplantation, which involves modifying the patient's own defective hematopoietic stem cells by inserting a correctly functioning human beta-globin gene, and then infusing these modified cells back into the patient.

LentiGlobin BB305 is currently being evaluated in both beta-thalassemia major and severe sickle cell disease, another type of blood disorder that affects hundreds of thousands of people every year.

If approved, this will be the first gene therapy product to be cleared by the U.S. FDA. Until now, only one gene therapy product, tiparvovec (Glybera, UniQure), has been approved in Europe.

Bluebird plans to talk to U.S. and EU regulators about starting a later-stage study instead of waiting for 24-month data to speed up the development, reports Business Week. The company will also need to discuss the amount and type of safety and efficacy data required to win regulatory approval.

David Davidson, M.D., CMO, Bluebird Bio, says, “We are on track to complete patient enrollment for the Northstar and HGB-205 studies in 2015, and as the clinical data continue to mature, we will work closely with medical experts, patient communities, and regulatory authorities to define the regulatory path forward for LentiGlobin.”